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Meta-analysis shows angiotensin receptor blocker use linked to increased risk of cancer

18th March 2022

Using an angiotensin receptor blocker (ARB) drug is associated with an increased risk of cancer, especially lung cancer, according to a meta-regression analysis of randomised trials by a cardiologist from the Department of Cardiology, Acibadem University Medical School, Istanbul, Turkey.

The angiotensin receptor blockers have been used clinically since 1995 and represent an effective class of antihypertensive agents with an excellent tolerability profile. Nevertheless, in 2018 the FDA in the US and the EMA in Europe, alerted health care professionals and patients of a voluntary recall of several drug products containing the active ingredient valsartan. This was due to the presence of an impurity, N-nitrosodimethylamine, which has been classified as a probable human carcinogen based on animal tests. After an initial evaluation, the EMA estimated that there could be one extra case of cancer for every 5000 patients taking the affected medicines at the highest valsartan dose (320 mg) every day for 7 years. Furthermore, the EMA has stated that there is a very low risk that nitrosamine impurities at the levels found in medicines could cause cancer in humans. However, a meta-analysis published in 2010, concluded that the use of an angiotensin receptor blocker is associated with a modestly increased risk of a new cancer diagnosis, though the authors also stated that it was not possible to draw conclusions about the exact risk of cancer associated with each particular drug.

For the present analysis, the author set out to re-examine the relationship between ARB use and the development of cancer, through an examination of information derived from randomised, controlled trials in which the drug class had been used. The study looked at cumulative exposure, i.e., the intensity and duration of exposure to the drug and specifically, the relationship with the development of lung cancer, which was found to be increased in the earlier meta-analysis.

Angiotensin receptor blocker use and cancer

A total of 15 randomised trials were included in the analysis with 74,021 patients given an ARB which included telmisartan (38.9%) and valsartan (33%).

In trials where the duration of use (reflecting cumulative exposure), exceeded 3 years, there was a statistically significant excess of new cancers in those assigned to an ARB (relative risk, RR = 1.12, 95% CI 1.02 – 1.24, p = 0.006). In contrast, this increased risk was absent trials where the drug was used for < 3 years. In relation to lung cancer, there was also an increased risk (RR = 1.21, 95% CI 1.02 – 1.44, p = 0.03) when the drugs were used for > 3 years but again, no increased risk when used for < 3 years.

Interestingly, there was also a higher cancer risk when an ARB was used alongside an angiotensin converting enzyme inhibitor for longer than 3 years (RR = 1.11, 95% CI 1.0 – 1.23, p = 0.05) and which, as before, was absent when used for a shorter period of time.

The author concluded that the risk of cancer and in particular lung cancer, increases with greater cumulative exposure to an angiotensin receptor blocker drug, adding that the widespread use of these drugs has profound implications for patients.

Citation
Sipahi I. Risk of cancer with angiotensin-receptor blockers increases with increasing cumulative exposure: Meta-regression analysis of randomized trials PloS One 2022